Patients with a compromised immune system are at risk for converting from latent tuberculosis infection (LTBI) to active tuberculosis (TB) infection. Multiple sclerosis (MS) therapies may put ...individuals with LTBI at higher risk of TB.
Patients at the Beth Israel Deaconess Medical Center MS Clinic were screened for TB as part of routine testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay (Cellestis Ltd) from 2013 to 2017. Patients were tested either before or during immunomodulatory therapy.
Four of 222 patients (1.8%; 95% CI, 0.1%-3.6%) had positive QFT-GIT results; three patients had risk factors for TB, having emigrated from TB-endemic countries or worked in the health care industry. Twenty-eight of 222 patients (12.6%) had an indeterminate assay result, and 75.0% of these occurred in patients taking dimethyl fumarate. Fingolimod, natalizumab, or anti-CD20 treatments showed 0% to 7.7% indeterminate results.
The prevalence of LTBI was 1.8% in the Beth Israel Deaconess Medical Center MS Clinic. Not all LTBI cases were associated with known risk factors for TB. Screening for LTBI before starting immunosuppressive agents for MS could help prevent activation of TB. Dimethyl fumarate use is associated with indeterminate QFT-GIT results, possibly due to functional effects on lymphocytes and levels of cytokines, such as interferon gamma. In contrast, fingolimod use was rarely associated with indeterminate QFT-GIT results despite a high rate of lymphopenia in virtually all patients.
The ecology, behaviour and genetics of our closest living relatives, the nonhuman primates, should help us to understand the evolution of our own lineage. Although a large amount of data has been ...amassed on primate ecology and behaviour, much less is known about the functional and evolutionary genetic aspects of primate biology, especially in wild primates. As a result, even in well-studied populations in which nongenetic factors that influence adaptively important characteristics have been identified, we have almost no understanding of the underlying genetic basis for such traits. Here, we report on the functional consequences of genetic variation at the malaria-related FY (DARC) gene in a well-studied population of yellow baboons (Papio cynocephalus) living in Amboseli National Park in Kenya. FY codes for a chemokine receptor normally expressed on the erythrocyte surface that is the known entry point for the malarial parasite Plasmodium vivax. We identified variation in the cis-regulatory region of the baboon FY gene that was associated with phenotypic variation in susceptibility to Hepatocystis, a malaria-like pathogen that is common in baboons. Genetic variation in this region also influenced gene expression in vivo in wild individuals, a result we confirmed using in vitro reporter gene assays. The patterns of genetic variation in and around this locus were also suggestive of non-neutral evolution, raising the possibility that the evolution of the FY cis-regulatory region in baboons has exhibited both mechanistic and selective parallels with the homologous region in humans. Together, our results represent the first reported association and functional characterization linking genetic variation and a complex trait in a natural population of nonhuman primates.
Acute and convalescent serum samples were collected from febrile inpatients identified at two hospitals in Moshi, Tanzania. Confirmed brucellosis was defined as a positive blood culture or a ≥ 4-fold ...increase in microagglutination test titer, and probable brucellosis was defined as a single reciprocal titer ≥ 160. Among 870 participants enrolled in the study, 455 (52.3%) had paired sera available. Of these, 16 (3.5%) met criteria for confirmed brucellosis. Of 830 participants with ≥ 1 serum sample, 4 (0.5%) met criteria for probable brucellosis. Brucellosis was associated with increased median age (P = 0.024), leukopenia (odds ratio OR 7.8, P = 0.005), thrombocytopenia (OR 3.9, P = 0.018), and evidence of other zoonoses (OR 3.2, P = 0.026). Brucellosis was never diagnosed clinically, and although all participants with brucellosis received antibacterials or antimalarials in the hospital, no participant received standard brucellosis treatment. Brucellosis is an underdiagnosed and untreated cause of febrile disease among hospitalized adult and pediatric patients in northern Tanzania.
Rituximab, a monoclonal antibody to CD20, is an effective treatment for relapsing remitting multiple sclerosis (MS) reducing relapse rate by at least 50% over time. Although the mechanism for this ...clinical benefit is unclear, rituximab depletes circulating B cells, which can perform antigen presentation and stimulation of T cells. Another anti-CD20 drug, ocrelizumab, has recently been FDA approved to treat both relapsing remitting and progressive forms of MS. While long-term effects of ocrelizumab use are essentially unknown, long-term use of rituximab has been associated with the development of progressive multifocal leukoencephalopathy (PML) at an incidence of approximately 1/25,000 in non-MS conditions. Serostatus for JC virus (JCV), the causative agent for PML, is an important risk stratification tool for natalizumab, but its utility in other MS treatments is uncertain. We found that rituximab use was associated with a reduction in JCV antibody index values in MS patients. Reductions in immunoglobulins, IgM in particular, are seen in concert with JCV antibody reductions. Physicians should exercise caution when using JCV antibody indices to assess any risk of PML for patients on rituximab.
CADASIL as a Multiple Sclerosis Mimic Bouley, Andrew J; Yaghi, Shadi
Medicine and health, Rhode Island,
11/2017, Letnik:
100, Številka:
11
Journal Article
CADASIL as a Multiple Sclerosis Mimic Bouley, Andrew J; Yaghi, Shadi
Rhode Island medical journal (2013),
2017-Nov-01, 20171101, Letnik:
100, Številka:
11
Journal Article
Recenzirano
Full article available at http://rimed.org/rimedicaljournal-2017-11.asp.
Background
Studies linking MRI findings in MS patients with obstructive sleep apnea severity are limited.
Objective
We conducted a retrospective study to assess MRI abnormalities associated with ...obstructive sleep apnea (OSA) in patients with multiple sclerosis (MS).
Methods
We performed retrospective chart review of 65 patients with multiple sclerosis who had undergone polysomnography (PSG) for fatigue as well as brain MRI. We measured the number of lesions in the brainstem and calculated the standardized third ventricular width (sTVW) as a measure of brain atrophy, and subsequently performed correlation analyses of the apnea-hypopnea index (AHI) with brainstem lesion location, sTVW, and Expanded Disability Status Scale (EDSS).
Results
MS Patients with OSA were significantly older and had a higher body mass index (BMI) and higher AHI measures than patients without OSA. After adjustment for covariates, significant associations were found between AHI and lesion burden in the midbrain (p < 0.01) and pons (p = 0.05), but not medulla.
Conclusions
Midbrain and pontine lesions burden correlated with AHI, suggesting MS lesion location could contribute to development of OSA.
Highlights • Spinal avm is a rare phenomenon. • Treatment modalities are varied, but there is no clear dominant approaches. • Conservative management is successful
We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the ...risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic.
A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney
test or analysis of variance for continuous variables and the χ
or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization.
Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support.
The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.
Clostridium difficile is a leading cause of antibiotic-associated diarrhea. The mechanisms underlying C. difficile expansion after microbiota disturbance are just emerging. We assessed the gene ...expression profile of C. difficile within the intestine of gnotobiotic mice to identify genes regulated in response to either dietary or microbiota compositional changes. In the presence of the gut symbiont Bacteroides thetaiotaomicron, C. difficile induces a pathway that metabolizes the microbiota fermentation end-product succinate to butyrate. The low concentration of succinate present in the microbiota of conventional mice is transiently elevated upon antibiotic treatment or chemically induced intestinal motility disturbance, and C. difficile exploits this succinate spike to expand in the perturbed intestine. A C. difficile mutant compromised in succinate utilization is at a competitive disadvantage during these perturbations. Understanding the metabolic mechanisms involved in microbiota-C. difficile interactions may help to identify approaches for the treatment and prevention of C. difficile-associated diseases.
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•Biassociation with a gut symbiont induces a C. difficile succinate-utilization operon•Succinate accumulates in the gut upon antibiotic treatment or motility disturbance•Succinate utilization enables C. difficile expansion in the perturbed gut•A C. difficile mutant compromised in succinate utilization is colonization defective
Nutrient resource partitioning by gut microbes is typically efficient. Ferreyra et al. demonstrate that upon antibiotic treatment or motility disturbance, succinate, an interspecies metabolic intermediate, transiently spikes to high levels. C. difficile induces a succinate-to-butyrate conversion pathway to take advantage of the succinate spike and expand during these gut perturbations.
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